Angiotensin converting enzyme homolog and uses therefor

Abstract

The present invention relates to the discovery of novel genes encoding an angiotensin converting enzyme, Angiotensin Converting Enzyme-2 (ACE-2). The invention provides therapeutics, prognostic and diagnostics methods for treating blood pressure related disorders as well as various types of allergic conditions, among others. Also disclosed are screening assays for identifying compounds for treating and preventing these conditions.

Description

RELATED APPLICATIONS[0001]This application claims priority to and is a continuation-in-part of U.S. application Ser. No. 08 / 989,299, filed on Dec. 11, 1997, U.S. application Ser. No. 09 / 163,648, filed on Sep. 30, 1998, U.S. application Ser. No. 09 / 407,427, filed on Sep. 29, 1999, and PCT Patent Application No.: PCT / US99 / 22976, filed on Sep. 29, 1999, incorporated herein in their entirety by this reference.BACKGROUND OF THE INVENTION[0002]Hypertension, or high blood pressure, is the most common disease affecting the heart and blood vessels. Statistics indicate that hypertension occurs in more than 50 million Americans. The prevalence of hypertension increases with age. Between 85 and 90% of cases are primary (i.e., essential) hypertension, i.e., a persistently elevated blood pressure that cannot be attributed to any particular organic cause. The remaining percentage of cases are secondary hypertension, i.e., elevated blood pressure having an identifiable underlying cause such as kidn...

AI Technical Summary

Benefits of technology

The present invention is based on the discovery of a novel gene encoding a novel human protein called angiotensin converting enzyme-2 (ACE-2). The ACE-2 gene is similar to other genes that encode angiotensin converting enzymes (ACEs). The ACE-2 gene is predominantly expressed in kidney and testis. The invention includes isolated nucleic acid molecules of the ACE-2 gene, as well as probes and primers that can be used for its detection. The invention also describes methods for producing ACE-2 proteins using expression vectors. The technical effects of the invention include the discovery of a new gene and its encoded protein, as well as new methods for detecting and producing ACE-2.

Problems solved by technology

Hypertension is of considerable concern because of the harm it can do to the heart, brain, and kidneys if it remains uncontrolled.

If it cannot meet the demands put on it, angina pectoris or even myocardial infarction may develop.

An untreated hypertensive patient is at great risk of developing disabling or fatal left ventricular failure, myocardial infarction, cerebral hemorrhage or infarction, or renal failure at early age.

Heart failure is a chronic or acute state that results when the heart is not capable of providing sufficient cardiac output to satisfy the metabolic needs of the body.

These symptoms are produced by diminished blood flow to the various tissues of the body and by accumulation of excess blood in the various organs, that results from the heart being incapable of pumping out the blood.

A major problem in CHF is the inability of the failing left ventricle to maintain a normal blood pressure, thus resulting in increased pre- and afterload, and leading to progressive ventricular dilation with wall remodeling.

Aldosterone is an adrenal cortex hormone that promotes the retention of salt and water by the kidneys and thus increases plasma volume, resulting in an increase in blood pressure.

However, ACE inhibitors in large doses can cause a variety of undesirable secondary effects including nephrotic syndrome, membraneous glomerulonephritis, nephritis, and leukopenia, as well as angioedema.

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